Medications to Avoid in the Elderly

The American Geriatrics Society (AGS) just released their 2012 update to their Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (65+ years old).

Quick summary: Medications to Avoid in the Elderly

Drug	Rationale	Recommend	Quality of Evidence	Str of Rec
Nitrofurantoin	Pulmonary tox Alternatives Lack of efficacy <60 mL/min	Avoid long term suppression; avoid if CrCl <60 mL/min	Moderate	Strong
Antipsychotics (conventional or atypical)	Increase CVA and CV mortality in dementia	Avoid unless danger to self/others and non pharm has failed	Moderate	Strong
Insulin, sliding scale	Hypoglycemia risk	Avoid	Moderate	Strong
Chlorpropamide Glyburide	Hypoglycemia risk	Avoid	High	Strong
Benzodiazepines (Short and long acting)	Risk cognitive effects and injury (fall/MVA); rare use appropriate eg benzo withdrawal	Avoid for treatment of insomnia, agitation, or delirium	High	Strong
Megestrol	Minimal effect on weight; risk of thrombotic events and death	Avoid	Moderate	Strong
Metoclopramide	EPS and TD	Avoid, unless gastroparesis	Moderate	Strong
Non-COX NSAIDs, oral	GI bleeding; Protection w/ PPIs or misoprostol	Avoid chronic use	Moderate	Strong
Non-BZD Hypnotics      (“z” drugs like ambient, soma, sonata)	Risk cognitive effects and injury (fall/MVA); same ADE as benzo’s	Avoid chronic use, >90 days	Moderate	Strong
Estrogens with or w/o progestin	Carcinogenic potential, lack of efficacy in dementia/CV dz prevention	Avoid oral and topical patch. Topical cream safe and effective for vaginal symptoms	High	Strong
Muscle Relaxants	Ineffective at tolerated doses, antichol, falls	Avoid	Moderate	Strong

Full List - Worth Reviewing

Acute Bacterial Sinusitis in Children

• The most common predisposing factors for acute bacterial sinusitis are:
• viral upper respiratory tract infection (URI)
• allergy
• Approximately 80% of episodes of acute bacterial sinusitis are preceded by a viral URI infection
• Children who attend day care are twice as likely to have sinusitis after a URI
• Diagnosis

• Treatment
• High-dose amoxicillin–clavulanate (90 mg/kg/d, divided bid) is first-line therapy for children
• in penicillin-resistant areas w/ resistance rates are of 10% or higher
• in day care
• > 2 years of age
• who have been hospitalized or treated with abx in the past month
• If the above risk factors are not present, standard-dose amoxicillin–clavulanate (40 mg/kg/d divided bid) is recommended
• Macrolides and TMP-SMX (bactrim) not recommended d/t high national rates of resistance
• Levofloxacin is recommended for children with h/o type I hypersensitivity reaction to PCN
• Recommended duration of therapy w/ amoxicillin–clavulanate or levofloxacin is 10-14 days in children

Reference: NEJM

AAP Says Benefits of Circumcision Outweigh Harms
A new policy statement from the AAP says the benefits of circumcision outweigh the harms

The benefits include:

• Lower risk for UTI before age 1 
• Reduced risk for STIs (e.g., HIV, HSV, HPV)
• Reduced risk for penile cancer 

The group says the procedures benefits justify access to those parents who desire it and warrants third-party payment for circumcision of male newborns.

The AAP did, however, stop short of recommending routine circumcision, saying that decision is best left to parents.  ACOG also endorses this policy statement.

Reference: AAP Policy Statement

New CDC recommendations about Hep C screening

One time hepatitis C screening for all patients born from 1945 to 1965

Guideline

• The Centers for Disease Control and Prevention recommends that all Americans born between 1945 and 1965 should have a one-time screening for hepatitis C virus (HCV), according to new finalized guidelines

• The CDC also recommends that all persons identified with HCV should receive a brief alcohol screening and intervention and be referred to the appropriate care and treatment services for HCV

Rationale

• About 2.7 to 3.9 million people in the U.S. are infected with HCV and approximately 45% to 85% of those with HCV are unaware that they are infected

• A CDC review found that hepatitis C mortality increased significantly from 1999 to 2007

• Nearly three quarters of these deaths occurred in baby boomers

• In addition, an NHANES study found a 3.25% prevalence in this age group

Reference: MMWR

CDC Updates Gonorrhea Treatment Guidelines

Bottom Line:

• The CDC no longer recommends cefixime (suprax) as a first-line treatment for gonorrhea 
• The only first line therapy now is ceftriaxone 250mg IM x1
• If ceftriaxone is unavailable, the updated guidelines allow use of cefixime (400 mg PO x1), but recommend a test-of-cure at 1 week.
  

The change was based on evidence that susceptibility to cefixime decreased among U.S. Neisseria gonorrhoeae isolates between 2006 and 2011.

In its 2010 treatment guidelines, the CDC recommended combination therapy with a cephalosporin (ceftriaxone or cefixime) plus oral azithromycin or doxycycline.

Reference: MMWR Article

Guidelines for Breast Cancer Screening

Reference:  http://www.nejm.org/doi/full/10.1056/NEJMcp1101540

Identify the Image

What's the diagnosis?

A 2-year-old girl was referred for an abnormal whitening (leukocoria) of the left pupil, as well as a divergent squint (Panel A). Her visual acuity was markedly impaired. Ophthalmologic examination revealed retinal detachment. Computed tomography showed left intraocular calcification (Panel B, arrow).

See comments for answer.

Statin Update

• Statin Induced Myopathy
• Myalgias are reported by 10 to 20% of patients who take statins
• The incidence of severe myotoxicity (CK > 10 times the upper limit of normal, associated with muscle symptoms leading to hospitalization) is estimated at 0.1 to 1.0%, or 0.4 to 1.1 per 10,000 patient-years.
• Risk factors for the development of a statin-associated myopathy:
• Concurrent medications
• e.g., fibrates and calcium-channel blockers
• Older age
• Hypothyroidism
• Hepatic dysfunction
• High BMI
• The risk of a statin-induced myopathy is dose-dependent
• The risk among patients who receive high-dose therapy is higher by a factor of 10 than the risk among patients who receive more moderate doses
• Simvastatin may be particularly notorious in this regard (high dose [greater than 40mg daily] = high risk of myopathy)
• Drugs that compete with the cytochrome P-450 system could augment statin myotoxicity
• Amlodipine, doxazosin, and finasteride all use this pathway and thus render patients vulnerable to the myotoxic effects of simvastatin
• Gemfibrozil poses an additional problem, since it may interfere with the hepatic uptake of simvastatin
• Concurrent therapy with statins and gemfibrozil has been associated with an increased risk of myopathy; in one study, the average incidence of rhabdomyolysis per 10,000 patient-years increased from 0.49 to 18.73

Reference: http://www.nejm.org/doi/full/10.1056/NEJMcpc1110052?query=BUL

• No More Routine Monitoring of LFTs for patients on Statins
• New FDA guidelines for statins released last week
• Recommendation for routine monitoring of LFTs in patients taking statins was removed.
• Labels now recommend that LFTs be checked before starting statin therapy and as clinically indicated thereafter.
• The FDA has concluded that serious liver injury with statins is rare and unpredictable in individual patients, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.

Reference: http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm

New Evidence About Osteoporosis Screening in Women - NEJM

Take home message from this study: Older women with BMD testing T scores greater than −1.50 have a low likelihood to develop osteoporosis and can defer retesting for 15 years, researchers concluded.

Women 65 and older are recommended to have bone mineral density (BMD) testing to screen for osteoporosis., but the evidence on appropriate intervals between testing is lacking.

This study followed 4957 women, 67 years of age or older, with normal BMD (T score at the femoral neck and total hip, −1.00 or higher) or osteopenia (T score, −1.01 to −2.49) and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis, prospectively for up to 15 years.

The BMD testing interval was defined as the estimated time for 10% of women to make the transition to osteoporosis before having a hip or clinical vertebral fracture, with adjustment for estrogen use and clinical risk factors. Transitions from normal BMD and from three subgroups of osteopenia (mild, moderate, and advanced) were analyzed with the use of parametric cumulative incidence models.

The estimated BMD testing interval was 16.8 years (95% confidence interval [CI], 11.5 to 24.6) for women with normal BMD, 17.3 years (95% CI, 13.9 to 21.5) for women with mild osteopenia, 4.7 years (95% CI, 4.2 to 5.2) for women with moderate osteopenia, and 1.1 years (95% CI, 1.0 to 1.3) for women with advanced osteopenia.

Bottom line suggested by this study:
Osteoporosis would develop in less than 10% of older, postmenopausal women during rescreening intervals of approximately 15 years for women with normal bone density or mild osteopenia, 5 years for women with moderate osteopenia, and 1 year for women with advanced osteopenia.

Reference: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1107142

ACOG Cervical Cancer Screening Guidelines

Under Age 21
- ACOG doesn't recommend pelvic examinations for girls < 21 unless they have been sexually active or have a medical complaint such as pelvic pain, vaginitis or irregular menstrual periods
- If a younger girl is sexually active, ACOG recommends a pelvic exam, Pap smear, and STD testing (including for chlamydia and gonorrhea) within three years following first intercourse

- All women between ages 19 and 64 who are sexually active should be tested for human immunodeficiency virus (HIV)

Age 21 to 30
- Pelvic examinations with Pap smears should begin at age 21 for women who have not been sexually active
- Thereafter, annual screening should continue up to age 30 (given higher risk for HPV in this group)
- Screen sexually active women 25 and under for chlamydia.  Urine based testing is adequate.

Over 30
- Screening can be cut back to every two or three years whenever a woman has three consecutive test results that were normal (provided she has no conditions that affect the immune system, was not exposed to the drug diethylstilbestrol (DES) while in utero (before birth), and has no other medical problems that require annual or semi-annual examinations)
- Routine physical pelvic exams should continue annually.

65 and Older
- Although routine pelvic exams should continue after age 65, under certain conditions, Pap smears can be discontinued at this point
- If three consecutive Pap smears are normal and there have been no abnormal results during the previous 10 years (with no history of cervical cancer, HIV or other conditions that affect the immune system, is at no risk of acquiring STDs, and was not exposed to DES) Pap smears can be eliminated from the annual exam

Exceptions
If a woman of any age has a complete hysterectomy for reasons other than cancer and has never had cervical cancer or abnormal Pap smears, Pap testing may be eliminated from routine pelvic exams, according to ACOG guidelines.

MKSAP Question

A 52-year-old man is evaluated for a 3-month history of perineal and suprapubic pain. He has experienced urinary frequency and dysuria for 4 to 6 weeks. The patient reports fatigue, insomnia, and low mood for the past 6 months. He has hypertension. Current medications are hydrochlorothiazide and acetaminophen as needed for pain.

On physical examination, temperature is normal, blood pressure is 138/80 mm Hg, and pulse rate is 78/min. BMI is 29. Abdominal examination is normal with mild suprapubic tenderness. The prostate is not enlarged; it is mildly tender without nodularity. Testicular examination is normal.
On laboratory study, urinalysis is normal, and urine culture is negative. Prostate-specific antigen level is 0.8 ng/mL (0.8 µg/L).

Which of the following is the most appropriate treatment for this patient?
A) Levofloxacin
B) Naproxen
C) Oxybutynin
D) Saw palmetto
E) Terazosin

See first comment for answer & explanation.

Identify the Image

What's the diagnosis?

This one's a softball, but good to see it to remind yourself what it looks like.  For a refresher on what a normal lateral neck film looks like, click here.

Answer in the first comment.
Reference: http://www.nejm.org/doi/full/10.1056/NEJMicm1009990

Primary Care for Childhood Survivors of Leukemia

Transition topic.  Fantastic NEJM article outlining primary care for childhood survivors of leukemia.
http://www.nejm.org/doi/full/10.1056/NEJMcp1103645?query=featured_home


Key Points:

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and 5-year survival rates in the United States have exceeded 70% for over two decades.

Adult survivors of childhood leukemia have increased risks of secondary cancers, cardiovascular disease, and other chronic illnesses, largely secondary to therapies for childhood cancer.

Clinicians caring for adult survivors of childhood leukemia should

• Request a treatment summary from the treating oncologist, a pediatric oncology program, or a local “survivor clinic.”

• Be aware that adults who received cranial radiotherapy as a component of treatment have increased risks of secondary tumors, stroke, growth hormone deficiency, and neurocognitive deficits.

• Check BMI, blood pressure, and lipids, since survivors of ALL have increased risks of obesity and associated metabolic derangements.

• Consider bone-density testing, since peak bone density is often reduced after childhood exposure to high-dose glucocorticoids and other therapies.

• Screen for left ventricular dysfunction in survivors who received anthracycline therapy, particularly if there was a high cumulative dose or treatment was before the age of 5 years.

Identify the Image

Just based on this image alone, what's the diagnosis in this 6 year old boy?

(answer in the first comment)

Breast Cancer Screening Guidelines

Given the data from randomized trials, which consistently show a 14 to 32% reduction in mortality from breast cancer with annual or biennial mammography in women 50 to 69 years of age, screening mammography should be recommended for women in this age group provided that their life expectancy is 5 years or more. For women 70 years of age or older, data from randomized trials are lacking, and the decision about screening should therefore be individualized on the basis of life expectancy and the patient's preference.

As for women in their 40s, there's not great consensus, and the decision should be individualized, with the recognition that the probability of a benefit is greater for women at higher risk.  For a woman in her 40s without risk factors, her chance of having invasive breast cancer over the next 8 years is about 1 in 80, and her chance of dying from it is about 1 in 400.

Mammographic screening every 2 years will detect two out of three cancers in women in their 40s and will reduce the risk of death from breast cancer by 15%. However, there is about a 40% chance that she will be called back for further imaging tests and a 3% chance that she will undergo biopsy, with a benign finding. Lifestyle modifications (e.g., weight control and avoidance of excessive alcohol consumption) that might lower her risk should also be discussed.

Reference: http://www.nejm.org/doi/full/10.1056/NEJMcp1101540

Case: Neck Swelling in an Adolescent

A previously healthy 13-year-old girl presents to the emergency department with a 2-week history of worsening sore throat and a 4-day history of left neck swelling, pain, and fever. Results of evaluation by a prior clinician at the onset of symptoms included a negative rapid streptococcal antigen test and a positive heterophile antibody test, prompting treatment with oral corticosteroids for 5 days as an anti-inflammatory medication. The girl now reports pain with swallowing, decreased oral intake, and left-sided head tilt for the past 24 hours.

On physical examination, the girl has a temperature of 38.4°C and appears to be in no acute distress. In addition, her heart rate is 91 beats/min, respiratory rate is 20 breaths/min, and blood pressure is 119/69 mm Hg. She has a warm, very tender, firm, anterior, left-sided 1.5-cm mass at the level of the thyroid gland. The mass moves when she swallows. Findings on the rest of her physical examination are normal.

Laboratory investigation reveals a white blood cell count of 17.2×10³/μL (17.2×10⁹/L) with 74% neutrophils and 14% lymphocytes, hemoglobin of 13 g/dL (130 g/L), and platelet count of 423×10³/μL (423×10⁹/L). C-reactive protein (CRP) measurement is elevated at 1.6 mg/dL (normal, 0.3 to 1.0 mg/dL). 

Images from a computed tomography (CT) scan of her neck with intravenous contrast enhancement are shown below.

What's the diagnosis?

***See first comment for answer.

MKSAP Question - Neurology

A 50-year-old man is evaluated for a 12-year history of slowly progressive left leg weakness and trouble ambulating. There is no history of transient neurologic symptoms. He has a history of hypertension, coronary artery disease, and chronic low back pain. Current medications are sublingual nitroglycerin, atenolol, aspirin, and occasional NSAIDs.

On physical examination, vital signs are normal. The patient has moderately severe spastic paraparesis that is worse on the left, with prominent circumduction of the left leg during ambulation. He requires a cane to ambulate 100 meters.

Cerebrospinal fluid analysis reveals the presence of oligoclonal bands.  MRIs of the brain and spine show lesions consistent with chronic multiple sclerosis.

Which of the following is the most appropriate treatment for this patient?

A) Glatiramer acetate

B) Interferon beta-1a

C) Natalizumab

D) Physical therapy


See first comment for correct answer with explanation.

UTI in Febrile Infants: Updated AAP Guidelines

A revised AAP clinical practice guideline on the diagnosis and management of the initial urinary tract infection (UTI) in febrile infants and young children is markedly different from the previous practice parameter published in 1999.  New data have become available in the past five years, with the findings prompting a reexamination of the older studies.  The notable changes are highlighted below:

1. Diagnosis: The criteria for diagnosis now include an abnormal urinalysis as well as a positive culture containing ≥ 50,000 colony forming units/milliliter of a urinary pathogen. The abnormal urinalysis helps distinguish true UTI from asymptomatic bacteriuria. Guidance also is provided regarding assessment of the likelihood of UTI to help determine which febrile infants clinicians should evaluate for UTI.
2. Treatment: Oral therapy is recognized as effective as parenteral therapy.
3. Imaging: Renal-bladder ultrasonography (RBUS) should be performed, but voiding cystourethrography (VCUG) no longer is recommended routinely after the first febrile UTI. Indications for VCUG include findings on RBUS that suggest the presence of high grade vesicoureteral reflux or the recurrence of a febrile UTI.
4. Follow-up: Emphasis should be on counseling families to seek medical evaluation promptly for UTI during future febrile illnesses.

The rationale for the biggest change — discouraging the routine performance of VCUGs — stems from analysis of the six recent randomized controlled trials of prophylaxis vs. no prophylaxis in young infants following a febrile UTI.

Prophylaxis was not demonstrated to be superior to no prophylaxis in preventing recurrence of febrile UTI in infants without reflux or in those with grades I-IV reflux. (In the studies, only five infants with grade V reflux were included, so the effectiveness of prophylaxis for infants with this grade of reflux is not known, but less than 1% of febrile infants with UTI have grade V reflux.)

Recurrent febrile UTI is less common among infants without high grade reflux, so waiting for the second UTI reduces the number of VCUGs performed by 90% and has a higher yield of infants with grades IV and V reflux. Studies of renal scarring suggest that waiting for the second UTI is acceptable and does not offset the benefit of sparing 90% of febrile infants with UTI the radiation, discomfort and cost of VCUG.

The figures in this updated guideline are worth scanning, including factors influencing the likelihood of UTI in febrile male & female infants; choices for parenteral and oral treatment of UTIs; sensitivity & specificity of diagnostic tests for UTI in infants; and a clinical practice guideline algorithm.

Reference: http://pediatrics.aappublications.org/content/128/3/595

Antihypertensive Choices

Thanks to Rita for this post, based on a recent encounter with a difficult to control hypertensive clinic patient:

He was already on Lopressor 100mg BID, Amlodipine 10mg daily, HCTZ 25mg daily combined with an ARB at maximum dose, and hydralazine 100mg TID.  He is at very high risk as he has already had a hemorrhagic stroke.  He also notes morning HTN.  

Reviewing Up to Date, we reminded ourselves a few things:

• Chlorthalidone is a better choice for a thiazide diuretic as it is likely a more potent anti-hypertensive agent, is definitely longer acting, and was the thiazide diuretic used in the ALLHAT study that showed thiazide superior to all other agents in preventing events.  It is very helpful for AM hypertension as the HCTZ likely has already worn off.  There is a more potent hypokalemic effect with chlorthalidone then HCTZ so monitoring is important as is with all diuretics
• The ACCOMPLISH study showed that for combination therapy, Amlodipine/ Benazepril was superior to other agents in preventing events and specifically was superior to Benazepril/ HCTZ which showed increased event rates.  The Up To Date authors actually recommend switching patients well controlled on ACE/ HCTZ to Amlodipine/ Benazepril. 
• Also our patient had cost issues with his ARB so was switched to a long acting ACE.
• In general young patients should be started on ACE or ARB’s as monotherapy with Bblocker as an alternative.  Of course remember in women of child bearing age to caution regarding ACE use.  Otherwise BBlockers should never be used as monotherapy.   Of course if there is a specific indication (post MI, CHF) B Blockers are indicated but would usually be combined with ACE-I.  There have been increased events in older patients with BBlockers.
• Older patients and African American patients should be given long acting CCB’s (like amlodipine) or thiazide diuretics (chlorthalidone preferred as above) as monotherapy
• Initial therapy of course also guided by comorbidities (DM or proteinuria:  ACE or ARB, Post MI, CHF, LV Dysfunction:  ACE-I/ BBlockers, etc.)

Note: Click link for great summary (in physician reference card form) of JNC 7 hypertension guidelines. And since I know you're all waiting with baited breath for it, JNC 8 is due out in 2012!  Mark your calendars!  --sds

Identify the Image

An 8-year-old boy was referred for evaluation of a mass in the midline of the ventral surface of the anterior tongue. The lesion had fluctuated in size since it was first noted 4 months earlier. He was otherwise asymptomatic, and his medical history revealed that he habitually bit his tongue. Examination of the tongue revealed a nontender, smooth-walled, translucent, bluish, fluctuant mass of approximately 8 mm in diameter that was resting on an opalescent base.


What's the diagnosis?
[see first comment to reveal answer]

Oral Diabetes Agents

Class	Mechanism of Action	Benefits	Risks/Concerns
Sulfonylureas	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; long duration of action	Extensive clinical experience; improved microvascular outcomes in UKPDS; low cost; once-daily dosing possible	Hypoglycemia; weight gain; potential impairment of cardiac ischemic preconditioning
Glyburide Glipizide Glimepiride
Glinides (meglitinides)	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; short duration of action	Target postprandial glucose; mimics physiologic insulin secretion	Hypoglycemia; weight gain; no long-term studies; expensive; frequent dosing (compliance an issue)
Repaglinide Nateglinide
Biguanides	Decrease hepatic glucose production	Extensive clinical experience; no hypoglycemia; weight loss or weight neutral; lipid and other nonglycemic vascular benefits; improved macrovascular outcomes; low cost; once-daily dosing available (sustained-release product)	Diarrhea, abdominal discomfort; many contraindications to consider, including serum creatinine >1.4 mg/dL (123.76 µmol/L) and lactic acidosis risk (rare); lowers vitamin B12 levels (without apparent effects on hematologic indices or neurologic function)
Metformin
α-Glucosidase inhibitors	Retard gut carbohydrate absorption	Target postprandial glucose; weight-neutral; nonsystemic	Flatulence, abdominal discomfort; frequent dosing (compliance); expensive
Acarbose Miglitol
Thiazolidinediones	Activate the nuclear receptor PPARγ, increasing peripheral insulin sensitivity. May also reduce hepatic glucose production	Address primary defect of T2DM; no hypoglycemia; lipid and other nonglycemic vascular benefits; probable decreased macrovascular outcomes with pioglitazone; greater durability of effectiveness; once-daily dosing	Edema and heart failure risk; weight gain; possible increased fracture risk in women; possible increased myocardial infarction risk with rosiglitazone; slow onset of action; expensive
Rosiglitazone Pioglitazone
Amylinomimetics	Activate amylin receptors, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	Weight loss	Nausea, vomiting; hypoglycemia risk when used with insulin; no long-term studies; injectable; expensive; frequent dosing (compliance)
Pramlintide
Incretin modulators	Activate GLP-1 receptors, increasing glucose-dependent insulin secretion, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	No hypoglycemia; weight loss	Nausea, vomiting; possible pancreatitis (rare); no long-term studies; injectable; expensive
GLP-1 mimetics Exenatide
DPP-IV inhibitors	Inhibit degradation of endogenous GLP-1 and GIP, thereby enhancing the effect of these incretins on insulin and glucagon secretion	No hypoglycemia; weight neutral; once-daily dosing	Possible urticaria/angioedema (rare); no long-term studies; expensive
Sitagliptin
Bile acid sequestrants	Bind cholesterol within bile acid; unknown mechanisms of antihyperglycemic effect	No hypoglycemia; weight neutral; lowers LDL-cholesterol	Constipation; may increase triglycerides; no long-term studies; expensive
Colesevelam

Reference: MKSAP 15
http://mksap15.acponline.org/tables/en_t07